Chromosome abnormalities associated with human tumors often represent genetic events that contribute to the development of malignancy. For example, the t(8;14) translocation observed in Burkitt's lymphoma activates the c-myc proto-oncogene by transposing it from its normal location on chromosome 8 into the immunoglobulin heavy chain locus on chromosome 14. A t(11;14) translocation is frequently observed in childhood T cell acute leukemia (T-ALL). As a consequence of the t(11;14) translocation, genetic material derived from the short arm of chromosome 11 is integrated into the T cell receptor alpha chain gene on the long arm of chromosome 14. The aims of this proposal are to isolate the breakpoint of the t(11;14) translocation and determine how DNA sequences from the short arm (11p) to chromosome 11 contribute to the development of T-ALL. Firstly, T cell receptor alpha chain gene probes will be used to clone the breakpoint of the t(11;14) translocation. Subsequently, the existence of a transcriptionally-active gene(s) amongst 11p sequences adjacent to the translocation breakpoint will be investigated, and the amino acid potential of this gene determined by nucleotide sequence analysis. The effect of chromosome translocation on expression of the 11p gene will be examined by comparing the RNA transcription patterns of normal T cells and T-ALL cells. Finally, the relationship between the 11p gene involved in childhood T-ALL and the recessive WT proto- oncogene implicated in Wilms' tumor and other childhood malignancies will be investigated.